When researchers first sequenced the human genome, they were astonished by how few traditional genes encoding proteins were scattered along those 3 billion DNA bases. Instead of the expected 100,000 or more genes, the initial analyses found about 35,000 and that number has since been whittled down to about 21,000. In between were megabases of “junk,” or so it seemed.
Most of a person’s genetic risk for common diseases such as diabetes, asthma and hardening of the arteries appears to lie in the shadowy part of the human genome once disparaged as “junk DNA.”This is wrong. Most of our genome is still junk in spite of what the ENCODE Consortium says.
Indeed, the vast majority of human DNA seems to be involved in maintaining individuals’ well being — a view radically at odds with what biologists have thought for the past three decades.
Those are among the key insights of a nine-year project to study the 97 percent of the human genome that’s not, strictly speaking, made up of genes.
The Encyclopedia of DNA Elements Project, nicknamed Encode, is the most comprehensive effort to make sense of the totality of the 3 billion nucleotides that are packed into our cells.
The project’s chief discovery is the identification of about 4 million sites involved in regulating gene activity. Previously, only a few thousand such sites were known. In all, at least 80 percent of the genome appears to be active at least sometime in our lives. Further research may reveal that virtually all of the DNA passed down from generation to generation has been kept for a reason.
“This concept of ‘junk DNA’ is really not accurate. It is an outdated metaphor,” said Richard Myers of the HudsonAlpha Institute for Biotechnology in Alabama.
Myers is one of the leaders of the project, involving more than 400 scientists at 32 institutions.
Another Encode leader, Ewan Birney of the European Bioinformatics Institute in Britain, said: “The genome is just alive with stuff. We just really didn’t realize that beforehand.”
“What I am sure of is that this is the science for this century,” he said. “In this century, we will be working out how humans are made from this instruction manual.”
After an initial pilot phase, ENCODE scientists started applying their methods to the entire genome in 2007. Now that phase has come to a close, signalled by the publication of 30 papers, in Nature, Genome Research and Genome Biology. The consortium has assigned some sort of function to roughly 80% of the genome, including more than 70,000 ‘promoter’ regions — the sites, just upstream of genes, where proteins bind to control gene expression — and nearly 400,000 ‘enhancer’ regions that regulate expression of distant genes.I expect encyclopedias to be much more accurate than this.
The real fun starts when the various data sets are layered together. Experiments looking at histone modifications, for example, reveal patterns that correspond with the borders of the DNaseI-sensitive sites. Then researchers can add data showing exactly which transcription factors bind where, and when. The vast desert regions have now been populated with hundreds of thousands of features that contribute to gene regulation. And every cell type uses different combinations and permutations of these features to generate its unique biology. This richness helps to explain how relatively few protein-coding genes can provide the biological complexity necessary to grow and run a human being.I think that much of this hype comes from a problem I've called The Deflated Ego Problem. It arises because many scientists were disappointed to discover that humans have about the same number of genes as many other species yet we are "obviously" much more complex than a mouse or a pine tree. There are many ways of solving this "problem." One of them is to postulate that humans have a much more sophisticated network of control elements in our genome. Of course, this ignores the fact that the genomes of mice and trees are not smaller than ours.
In what should be another blow to the hubris of human intellect, we have a new entry in the long and ever growing list of “Really Big Things Scientists Believed” that turned out be wrong. This one is about DNA, that magical strand of just four amino acids, Adenine paired with Thymine, Cytosine paired with Guanine, millions of those A-T and C-G pairs linked together in various combinations to make the genes that spit out the blueprints for the proteins that make us. Or so science believed.As I said earlier, this is making my life very complicated. It's going to take a lot of effort to undo the damage caused by the ENCODE scientists and the science writers who fell for their scam.
The problem was that, the ‘genes’ sections of DNA that coded for proteins only came to about 1.5% of the whole 2 meter-long strand. For decades molecular biologists didn’t know what the rest of the DNA…as in, nearly all of it…does. So, in a remarkable stroke of intellectual arrogance, they dismissed it as ‘junk’. Actually, the drier academics simply called it ‘non-coding DNA’. A Japanese scientist named Susumu Ohno called it junk, and the word stuck because, basically, scientists had no explanation for what most of DNA was for. So they assumed it was left over from evolution, had no current function, and was, literally, junk. As Francis Crick, one of the Nobel Prize winners for helping discover the structure of DNA, put it, non-coding DNA has “little specificity and conveys little or no selective advantage to the organism”. Right. As though nature would waste that much energy.
Well, there’s going to be a lot of editing on Wikipedia in the days and weeks to come, and it’s time to reprint the basic biology textbooks, because extensive research into the mystery of what most of DNA is doing there has discovered that the ‘junk’ isn’t junk at all. Most of it has all sorts of jobs. Science Journalist Ed Yong has written a wonderful summary of this work here.
... we also uncovered some surprises that challenge the current dogma on biological mechanisms. The generation of numerous intercalated transcripts spanning the majority of the genome has been repeatedly suggested, but this phenomenon has been met with mixed opinions about the biological importance of these transcripts. Our analyses of numerous orthogonal data sets firmly establish the presence of these transcripts, and thus the simple view of the genome as having a defined set of isolated loci transcribed independently does not seem to be accurate. Perhaps the genome encodes a network of transcripts, many of which are linked to protein-coding transcripts and to the majority of which we cannot (yet) assign a biological role. Our perspective of transcription and genes may have to evolve and also poses some interesting mechanistic questions. For example, how are splicing signals coordinated and used when there are so many overlapping primary transcripts? Similarly, to what extent does this reflect neutral turnover of reproducible transcripts with no biological role?This didn't stop the hype. The results were widely interpreted as proof that most of our genome has a function and the result featured prominently in the creationist literature.
Blogs have been around for more than a decade but it's still not clear what purpose they serve (if any). We still don't know how to distinguish a science blog from other types of blogs—perhaps it's foolish to try.The earliest science bloggers were those who started out doing something else online – updating their websites frequently, or participating in Usenet groups – then moving their stuff to blogging software once it became available in the late 1990s and early 2000s.In my case the usenet groups were talk.origins and sci.bio.evolution. Both of those groups are hosted on a server in my office; talk.origins is still very active but sci.bio.evolution isn't.
As much of the early online activity focused on countering anti-science claims, e.g., the groups battling against Creationism on Usenet, it is not surprising that many of the early science bloggers came out of this fora and were hardly distinguishable in form, topics and style from political bloggers. They brought a degree of Usenet style into their blogs as well: combative and critical of various anti-science forces in the society.
Whether you need to learn the basics or fine tune the dark art of science communication, this half day workshop is for you. Come for insider advice from a group of North America’s top science communicators. The session will open with evolutionary ecologist Tom Sherratt talking about his experience with the media and why he does it. The panellists will introduce an area of journalism and discuss their experiences with interviewing researchers. Then the panel discussion will expand on some of the challenges scientists face and the practical communication solutions. Finally a break-out session will allow for an interactive round table letting participants choose a topic of particular interest (how to give an interview, how to pitch a science book to a publisher, 101 for scientists using social media). The workshop will conclude with a networking session between fellow science communicators and the panellists. By the end, delegates can expect to have built a strategy as to how to effectively approach and handle different media opportunities (such as TV, radio, print & social media) and also leave with a handout of useful tips.The panelists were ....
Researchers from the University of Toronto, the Royal Ontario Museum (ROM) and the University of Cambridge have confirmed that a 505 million-year-old creature, found only in the Burgess Shale fossil beds in Canada’s Yoho National Park, is the most primitive known vertebrate and therefore the ancestor of all descendant vertebrates, including humans.The headline is wrong. Pikaia is a chordate but not a vertebrate as the quotations from the researchers make clear. The press release from Cambridge is only a bit better [Humans' ancient ancestor revealed - as a 505 million-year-old 'eel']
The research team’s analysis proves the extinct Pikaia gracilens is the most primitive member of the chordate family, the group of animals that today includes fish, amphibians, birds, reptiles and mammals. Their study is based on the analysis of 114 specimens and is published in the British scientific journal Biological Reviews.
“The discovery of myomeres is the smoking gun that we have long been seeking,” said the study’s lead author, Professor Simon Conway Morris of the University of Cambridge. “Now with myomeres, a nerve chord, a notochord and a vascular system all identified, this study clearly places Pikaia as the planet’s most primitive chordate. So, next time we put the family photograph on the mantle-piece, there in the background will be Pikaia."Furthermore, this really isn't news. Pikaia was featured in Stephen Jay Gould's book Wonderful Life published in 1989. Even then, Pikaia gracilens was thought to be a chordate similar in broad features to the cephalochordate (non-vertebrate chordate) Amphioxus. This classification was attributed to Simon Conway Morris in 1979. The Wikipedia article [Pikaia] points out that this classification was not universally accepted.
Conway Morris, S. and Caron, J-B (2012) Pikaia gracilens Walcott, a stem-group chordate from the Middle Cambrian of British Columbia. Biological Reviews. Article first published online: 4 MAR 2012 [doi: 10.1111/j.1469-185X.2012.00220.x]
For newly arisen introns having no functional significance for the products of their host genes, the primary force opposing their ability to spread throughout a population is their excess mutation rate to defective allele(s), and because this force is expected to be quite weak, selection will be ineffective in preventing intron colonization in populations experiencing substantial levels of random genetic drift.The selection coefficient for intron deletion has to be above a certain threshold in order to prevent introns from spreading. This threshold depends on the population size: in large populations the deleterious effect of introns is sufficient to ensure that they will be kept to a minimum, or eliminated entirely.
Lynch, M. (2010) Rate, molecular spectrrum, and consequences of human mutation. Proc. Natl. Acad. Sci. USA 107:961-968. [doi: 10.1073/pnas.0912629107]
1. What would we do for fun if we didn't have Chris Mooney? We'd have to pick of the creationists all the time and thatgets boring.
This incident, like a handful before it and probably more to come, has raised the profile of science blogging and the freedom that the Internet offers to express an opinion and reach a broad audience. Yet it also raises questions about the validity of unfettered opinion and personal bias, and the ability to publish online with little editorial oversight and few checks and balances.It's true that there's no editorial oversight on science blogs. It's not quite true that there are no checks and balances since most science bloggers read and comment on each other's posts and bad science bloggers are easily exposed (e.g. creationist sites).
[HatTip: Jarry Coyne: An EMBO report on science blogging]
A recent paper in Molecular Cell involved the study of nucleosome assembly in vitro (Torigoe et al. 2011). The authors were looking for intermediate stages in the assembly of nucleosome after DNA replication. Here's the abstract of their paper ...
Chromatin assembly involves the combined action of histone chaperones and ATP-dependent motor proteins. Here, we investigate the mechanism of nucleosome assembly with a purified chromatin assembly system containing the histone chaperone NAP1 and the ATP-dependent motor protein ACF. These studies revealed the rapid formation of a stable nonnucleosomal histone-DNA intermediate that is converted into canonical nucleosomes by ACF. The histone-DNA intermediate does not supercoil DNA like a canonical nucleosome, but has a nucleosome-like appearance by atomic force microscopy. This intermediate contains all four core histones, lacks NAP1, and is formed by the initial deposition of histones H3-H4. Conversion of the intermediate into histone H1-containing chromatin results in increased resistance to micrococcal nuclease digestion. These findings suggest that the histone-DNA intermediate corresponds to nascent nucleosome-like structures, such as those observed at DNA replication forks. Related complexes might be formed during other chromatin-directed processes such as transcription, DNA repair, and histone exchange.Interesting but hardly Earth-shattering. More work needs to be done to confirm this result and see if it's significant in vivo. At least that's what you would think if you just looked at the paper.
Basic biology textbooks may need a bit of revising now that biologists at UC San Diego have discovered a never-before-noticed component of our basic genetic material.
According to the textbooks, chromatin, the natural state of DNA in the cell, is made up of nucleosomes. And nucleosomes are the basic repeating unit of chromatin.
That's correct. All the textbooks have a diagram similar to the one shown here from my textbook. It shows the organization of nucleosome core particles and the completed nucleosome on DNA.
"This novel particle was found as a precursor to a nucleosome," said James Kadonaga, a professor of biology at UC San Diego who headed the research team and calls the particle a "pre-nucleosome." "These findings suggest that it is necessary to reconsider what chromatin is. The pre-nucleosome is likely to be an important player in how our genetic material is duplicated and used."This is mostly hype and none of this speculation is found in the actual paper. Unfortunately, this sort of press release has become the norm and that's got to stop.
The biologists say that while the pre-nucleosome may look something like a nucleosome under the microscope, biochemical tests have shown that it is in reality halfway between DNA and a nucleosome.
These pre-nucleosomes, the researchers say, are converted into nucleosomes by a motor protein that uses the energy molecule ATP.
"The discovery of pre-nucleosomes suggests that much of chromatin, which has been generally presumed to consist only of nucleosomes, may be a mixture of nucleosomes and pre-nucleosomes," said Kadonaga. "So, this discovery may be the beginning of a revolution in our understanding of what chromatin is."
1. It even seemed important enough for Richard Dawkins.net: Biologists' Discovery May Force Revision of Biology Textbooks: Novel Chromatin Particle Halfway Between DNA and a Nucleosome.
I teach a course called "Scientific Controversies and Misconceptions." (You won't be surprised to learn that one of the main topics is evolution vs. creationism.) The most difficult part of the course is teaching students to be skeptical about the scientific literature. The reason why this is difficult is because the main focus is evidence based reasoning and science is an important way to gather reliable evidence. It's uncomfortable to have to mention that errors and fraud are not uncommon in the scientific literature.
Kalliopi Monoyios is a science illustrator who works at the University of Chicago. She's the artist behind Your Inner Fish and Why Evolution Is true. She has a blog called Symbiartic where she writes about the trials and tribulations of Confession time. Illustrators are people, too. And by that I mean they bring assumptions to the table at the outset of every project. There’s no avoiding it – no matter how educated and experienced you are, you can’t know it all. That is why it is so critical for researchers and editors to be intimately involved in every draft of the drawings they commission and publish. This may sound like a mega no-brainer, especially if you’re an editor or art director in a field other than in the sciences who is accustomed to working intimately with illustrators to get what you want. But in my experience illustrating two popular non-fiction science books, illustrations are treated as icing on the cake and are glossed over by fact checkers and editors who otherwise comb manuscripts for errors. Illustrating Your Inner Fish is a prime example. The manuscript went through four drafts of revisions with at least two specialized scientific editors. And yet this gaffe made it through:I know exactly how she feels but even multiple expert reviewers won't save you. When we're writing a textbook we take care to review the text and figures together and we pay just as much attention to the figures as we do to the text. For the most recent edition—about to be sent to the printer—the pages were reviewed by me, my coauthor Marc Perry, our developmental editor Michael Sypes (University of Arizona), content reviewer Barry Ganong (Mansfield University), and accuracy reviewers Scott Lefler (Arizona State University) & Kathleen Nolta (University of Michigan). That's six pairs of expert eyes that look at every page.
1. I'll post the correct version in a few days.
Field D, Amaral-Zettler L, Cochrane G, Cole JR, Dawyndt P, et al. 2011 The Genomic Standards Consortium. PLoS Biol 9(6): e1001088. doi:10.1371/journal.pbio.1001088.I'm interested in this sort of thing since back in the olden days (1993) I spent a bit of time at GenBank exploring annotation issues with a view to correcting the growing number of errors that were being propagated in online databases.
Abstract
A vast and rich body of information has grown up as a result of the world's enthusiasm for 'omics technologies. Finding ways to describe and make available this information that maximise its usefulness has become a major effort across the 'omics world. At the heart of this effort is the Genomic Standards Consortium (GSC), an open-membership organization that drives community-based standardization activities, Here we provide a short history of the GSC, provide an overview of its range of current activities, and make a call for the scientific community to join forces to improve the quality and quantity of contextual information about our public collections of genomes, metagenomes, and marker gene sequences.
The Internet has resulted in a Cambrian explosion of productivity and data sharing through the adoption of a huge stack of agreed-upon protocols (standards) that allow many devices and programs to communicate to the transformative benefit of the everyday user [26]. Enabling access to user-generated content is key to harnessing the resources of a distributed community: Flickr has over 5 billion photographs uploaded, and Wikipedia has over 3.5 million English articles as of this writing. Standards for organizing sequence data will be similarly needed as sequencing instruments themselves, especially as these instruments are more and more commoditized and owned by individuals rather than institutions.I'm sad to find this sort of content-free language creeping into scientific journals. We've been spared up to now but it looks like the 23 scientists listed as authors feel comfortable with this new style of writing.
